The interaction of malignant cells with blood-vessel endothelial cells and their underlying basement membrane is an important step in the development of secondary metastases. We investigated the interactions of highly metastatic human tumor cells, the A-549 adenocarcinoma of the lung, with cultured endothelial cells (EC) and their extracellular matrix (ECM). We studied the adhesion patterns of the A-549 tumor cells to EC and ECM under static and flow conditions. Our results provide evidence that tumor-cell adhesion depends not only on the characteristics of the tumor cells themselves, but also on the properties of the EC and ECM. Our results also indicate that tumor-cell adhesion to ECM is shear-rate-dependent, and that it is partially modulated by fibronectin. Moreover, our results suggest that the arg-gly-asp (RGD) common adhesion receptor site is also involved in the adhesion of the A-549 cells to EC and ECM.